A global sampling approach to designing and reengineering RNA secondary structures. - Archive ouverte HAL Access content directly
Journal Articles Nucleic Acids Research Year : 2012

A global sampling approach to designing and reengineering RNA secondary structures.

(1, 2) , (1) , (3, 4) , (1) , (1) , (1, 2) , (1, 2)
1
2
3
4

Abstract

The development of algorithms for designing artificial RNA sequences that fold into specific secondary structures has many potential biomedical and synthetic biology applications. To date, this problem remains computationally difficult, and current strategies to address it resort to heuristics and stochastic search techniques. The most popular methods consist of two steps: First a random seed sequence is generated; next, this seed is progressively modified (i.e. mutated) to adopt the desired folding properties. Although computationally inexpensive, this approach raises several questions such as (i) the influence of the seed; and (ii) the efficiency of single-path directed searches that may be affected by energy barriers in the mutational landscape. In this article, we present RNA-ensign, a novel paradigm for RNA design. Instead of taking a progressive adaptive walk driven by local search criteria, we use an efficient global sampling algorithm to examine large regions of the mutational landscape under structural and thermodynamical constraints until a solution is found. When considering the influence of the seeds and the target secondary structures, our results show that, compared to single-path directed searches, our approach is more robust, succeeds more often and generates more thermodynamically stable sequences. An ensemble approach to RNA design is thus well worth pursuing as a complement to existing approaches. RNA-ensign is available at http://csb.cs.mcgill.ca/RNAensign.

Dates and versions

hal-00733924 , version 1 (20-09-2012)

Identifiers

Cite

Alex Levin, Mieszko Lis, Yann Ponty, Charles W O'Donnell, Srinivas Devadas, et al.. A global sampling approach to designing and reengineering RNA secondary structures.. Nucleic Acids Research, 2012, 40 (20), pp.10041-10052. ⟨10.1093/nar/gks768⟩. ⟨hal-00733924⟩
396 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More